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Background: Clinical trial findings on cholinesterase inhibitors (ChEIs) for mild cognitive impairment (MCI) are inconclusive, offering limited support for their MCI treatment. Given that nearly half of amnestic MCI cases lack cerebral amyloid-ß (Aß) deposition, a hallmark of Alzheimer's disease; this Aß heterogeneity may explain inconsistent results. Objective: This study aimed to assess whether Aß deposition moderates ChEI effects on amnestic MCI cognition. Methods: We examined 118 individuals with amnestic MCI (ages 55-90) in a longitudinal cohort study. Baseline and 2-year follow-up assessments included clinical evaluations, neuropsychological testing, and multimodal neuroimaging. Generalized linear models were primarily analyzed to test amyloid positivity's moderation of ChEI effects on cognitive change over 2 years. Cognitive outcomes included Mini-Mental Status Examination score, the total score of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery, and Clinical Dementia Rating-sum of boxes. Results: The analysis found no significant ChEI use x amyloid positivity interaction for all cognitive outcomes. ChEI use, irrespective of Aß status, was associated with more cognitive decline over the 2-year period. Conclusions: Aß pathology does not appear to moderate ChEI effects on cognitive decline in MCI.
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BACKGROUND: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aß) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aß and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aß and tau deposition. METHODS: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. RESULTS: No associations were found between either thyroid hormones or TSH and Aß and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aß on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aß deposition was not significant, whereas the interaction between fT3 and Aß deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aß and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aß on tau deposition. CONCLUSION: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aß and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aß-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.
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Péptidos beta-Amiloides , Tomografía de Emisión de Positrones , Hormonas Tiroideas , Proteínas tau , Humanos , Masculino , Femenino , Anciano , Proteínas tau/sangre , Proteínas tau/metabolismo , Estudios Transversales , Hormonas Tiroideas/sangre , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/sangre , Persona de Mediana Edad , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Tiroxina/sangre , Tirotropina/sangre , Estudios de CohortesRESUMEN
Depression and osteoporosis are common diseases in dialysis patients. In addition, patients with osteoporosis are more susceptible to depression. Contrary to previous anti-osteoporosis agents, denosumab and romosozumab could be used in dialysis patients and have similar action mechanisms for blocking RANKL. RANKL causes bone resorption after binding RANKL, but binding with OPG leads to suppress of bone resorption. In recent mice study, inhibition of RANKL with denosumab improved depressive-like phenotype. Besides, it was found that OPG was associated with depression. Therefore, this study aimed to investigate the association of depressive symptoms with RANKL and OPG in hemodialysis patients. We conducted a cross-sectional study with a total of 172 hemodialysis patients. The participants were measured for plasma RANKL, OPG, MMP-2, and MMP-9 levels. Logistic regression analysis was performed to evaluate the effect of RANKL and OPG on the presence of depressive symptoms. The depressive symptoms were observed in 90 (52.3%) subjects. RANKL tertile 3 had negative association with BDI score (ß - 4.527, 95% CI - 8.310 to - 0.743) in univariate analysis, and this association persisted even after multivariate adjustments (ß - 5.603, 95% CI - 9.715 to -1.491) in linear regression. In logistic regression between RANKL tertiles and depressive symptoms, RANKL tertile 3 had significantly lower unadjusted OR (0.40, 95% CI 0.19-0.86), and multivariate-adjusted OR (0.31, 95% CI 0.12-0.82) for depressive symptoms. OPG was not significantly associated with depressive symptoms. Higher plasma RANKL concentrations were significantly associated with lower depressive symptoms in HD patients.Trial registration WHO registry, No. KCT0003281, date: January 12, 2017.
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Depresión , Ligando RANK , Diálisis Renal , Humanos , Ligando RANK/sangre , Femenino , Masculino , Diálisis Renal/efectos adversos , Persona de Mediana Edad , Depresión/sangre , Estudios Transversales , Anciano , Osteoprotegerina/sangre , Osteoporosis/sangreRESUMEN
BACKGROUND: Lessons learned from the Household Humidifier Disinfectant Tragedy (HHDT) in Korea, which poisoned thousands of citizens over a period of years, necessitated an examination of national poison prevention and surveillance systems. The objectives of this study are to identify essential changes needed in chemical poisoning prevention regulations and surveillance systems for effective poison control by comparing recent trends in international poison control center (PCC) operations, and to delineate the critical elements for establishing a state-of-the-art poison control surveillance system in Korea based on recent advances in PCCs with toxicovigilance. METHODS: A comprehensive review of Korea's regulatory and surveillance systems for chemical health hazards, with a focus on household products under the HHDT, was conducted. A review of toxicovigilance systems in major countries shows that creating an effective national PCC requires key elements: a centralized database of toxic substances and poisoning cases, mandatory or voluntary reporting of poisoning cases, real-time alerts, collaboration among health organizations, and targeted follow-up of poisoned individuals. RESULTS: Significant deficiencies in Korea's legislation, toxicological data management, and poisoning surveillance systems, explained the inadequate response of the Korean government to the HHDT for nearly 17 years until the end of 2011. Based on a review of PCC toxicovigilance systems in major countries, a national framework with five core components is recommended for establishing a modern comprehensive Korea PCC system with toxicovigilance capacity. The core components include establishment of a centralized database of toxic substances information and clinical poisoning cases, implementation of mandatory or permissive reporting of poisoning cases, real-time alert mechanisms, collaborative systems among health-related organizations, and clinical follow-up of poisoned sub-groups. CONCLUSION: A rationale and framework for a state-of-the-art national Korean PCC with toxicovigilance is justified and offered. This proposed system could assist neighboring countries in establishing their own sophisticated, globally integrated PCC networks.
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Desinfectantes , Humidificadores , Intoxicación , Humanos , República de Corea/epidemiología , Desinfectantes/efectos adversos , Intoxicación/epidemiología , Intoxicación/prevención & control , Intoxicación/etiología , Centros de Control de IntoxicacionesRESUMEN
Importance: Many epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood. Objective: To examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aß) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults. Design, Setting, and Participants: This was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aß deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aß deposition were included. Exposure: Plasma leptin levels as assessed by enzyme-linked immunosorbent assay. Main Outcomes and Measures: Baseline levels and longitudinal changes of global Aß and AD-signature region tau deposition measured by PET scans. Results: Among the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aß deposition (ß = -0.04; 95% CI, -0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (ß = -0.02; 95% CI, -0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (ß = -0.06; 95% CI, -0.11 to -0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aß deposition (ß = 0.006; 95% CI, 0.00-0.02; P = .27). Conclusions and Relevance: The present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aß and tau deposition.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Leptina , Proteínas tau , Humanos , Leptina/sangre , Femenino , Masculino , Anciano , Enfermedad de Alzheimer/sangre , Estudios Longitudinales , Estudios Transversales , Péptidos beta-Amiloides/sangre , Proteínas tau/sangre , Tomografía de Emisión de Positrones , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , República de Corea/epidemiología , Anciano de 80 o más Años , Disfunción Cognitiva/sangre , Biomarcadores/sangre , Persona de Mediana EdadRESUMEN
INTRODUCTION: End-stage renal disease (ESRD) is a growing disease worldwide, including Korea. This is an important condition that affects patient outcome. To provide optimal management for mineral disturbance, vascular calcification, and bone disease in ESRD patients, the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) study was conducted by enrolling Korean dialysis patients. METHODS: Sixteen university-affiliated hospitals and one Veterans' Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive patients on dialysis between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of the patients were performed, and their biospecimens were collected according to the study protocol. The primary outcomes were the occurrence of major adverse cardiovascular events, invasive treatment for peripheral artery disease, and osteoporotic fractures. The secondary outcomes were hospitalization for cerebrovascular disease or progression of abdominal aortic calcification. Participants will be assessed for up to 3 years to determine whether primary or secondary outcomes occur. RESULTS: Between May 2019 and January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of the subjects was 60.4 ± 12.3 years. Males accounted for 57.7% of the total population. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. CONCLUSION: This nationwide, multicenter, prospective cohort study focused on chronic kidney disease-mineral and bone disorder and aimed to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.
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Fallo Renal Crónico , Diálisis Renal , Calcificación Vascular , Humanos , Diálisis Renal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea/epidemiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Anciano , Estudios de Cohortes , Densidad ÓseaRESUMEN
BACKGROUND: Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. METHODS: A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. RESULTS: Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. CONCLUSION: Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.
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BACKGROUND: Growing evidence suggests that not only cerebrovascular disease but also Alzheimer's disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aß) and tau deposition, and WMHs through longitudinal approach. METHODS: Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aß deposition, [18F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aß or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aß or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aß or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies. RESULTS: Baseline Aß deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aß or tau deposition for 2 years. We also found a significant interaction effect between baseline Aß deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aß deposition was associated with increase of WMH volume over 2 years in female, but not in male. CONCLUSIONS: Our findings suggest that Aß deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aß increase. The results also did not support any direction of influence between tau deposition and WMHs.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Sustancia Blanca , Humanos , Masculino , Femenino , Anciano , Enfermedad de Alzheimer/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Imagen por Resonancia Magnética , Disfunción Cognitiva/patologíaRESUMEN
OBJECTIVES: Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population. METHODS: We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73 m2), group 2 (eGFR ≥60 to <90 mL/min/1.73 m2), and group 3 (eGFR <60 mL/min/1.73 m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019. RESULTS: In multivariate analysis, group 2 exhibited a 26% higher risk of developing lung cancer than group 1 (HR, 1.26; 95% CI, 1.19 to 1.35). Furthermore, group 3 demonstrated a 72% elevated risk of lung cancer relative to group 1 (HR, 1.72; 95% CI, 1.58 to 1.89). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.93; 95% CI, 1.37 to 6.24). CONCLUSIONS: Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.
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Tasa de Filtración Glomerular , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , República de Corea/epidemiología , Femenino , Persona de Mediana Edad , Adulto , Anciano , Incidencia , Factores de Riesgo , Estudios de Cohortes , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
Hemodialysis patients are susceptible to cardiovascular remodeling, which increases the risk of cardiovascular morbidity and mortality. Circulating extracellular matrix (ECM)-associated molecules increase during cardiovascular remodeling and can be potential biomarkers of adverse cardiovascular outcomes. However, their clinical significance in patients undergoing hemodialysis remain unclear. This study aimed to elucidate the association between circulating ECM-associated molecules and cardiovascular outcomes in patients undergoing hemodialysis. To this end, we measured levels of plasma matrix metalloproteinase (MMP)-2, MMP-9, tenascin-C, and thrombospondin-2 in 372 patients with hemodialysis. Plasma MMP-2 levels were significantly higher in patients with future cardiovascular events than in those without future cardiovascular events (P = 0.004). All measured molecules had significant correlations with amino-terminal pro-brain natriuretic peptide levels, but the correlation coefficient was the strongest for plasma MMP-2 (rho = 0.317, P < 0.001). High plasma MMP-2 levels were predictive of left ventricular (LV) diastolic dysfunction (adjusted odds ratio per a standard deviation increase = 1.48, 95% confidence interval [CI] = 1.05-2.08) and were independently associated with an increased risk of composite cardiovascular events (adjusted hazard ratio per a standard deviation increase = 1.30, 95% CI = 1.04-1.63). In conclusion, high plasma MMP-2 levels are associated with LV diastolic dysfunction and an increased risk of adverse cardiovascular outcomes in hemodialysis patients.
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Bisphosphonates are commonly used to treat osteoporosis. While renal toxicity is common with pamidronate and zoledronate, few ibandronate-related cases are reported. We describe a rare case of ibandronate-associated nephrotoxicity. An 88-year-old woman was admitted for edema. She had been receiving intravenous ibandronate treatment for postmenopausal osteoporosis and had no other diagnosed diseases. She was presented with proteinuria, hypoalbuminemia (1.9 g/dL), and an elevated serum creatinine level (1.8 mg/dL). Renal biopsy revealed podocyte disease, favoring a diagnosis of focal segmental glomerulosclerosis. She was treated with diuretics, tacrolimus, and fimasartan. Steroids were avoided due to severe osteoporosis. Three months later, the edema had subsided and the laboratory findings had improved (serum albumin 3.5 g/dL, serum creatinine 0.97 mg/dL). This case emphasizes the importance of careful monitoring of proteinuria and renal function during ibandronate treatment. In older adult patients, kidney biopsy and immunosuppressive treatment may be considered based on physical activity and underlying diseases.
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Object: Effective triage of febrile patients in the emergency department is crucial during times of overcrowding to prioritize care and allocate resources, especially during pandemics. However, available triage tools often require laboratory data and lack accuracy. We aimed to develop a simple and accurate triage tool for febrile patients by modifying the qSOFA score. Methods: We retrospectively analyzed data from 7,303 febrile patients and created modified versions of qSOFA using factors identified through multivariable analysis. The performance of these modified qSOFAs in predicting in hospital mortality and intensive care unit (ICU) admission was compared using the area under the receiver operating characteristic curve (AUROC). Results: Through multivariable analysis, the identified factors were age (A), male sex (M), SpO2 (S), and lactate levels (L). The AUROCs of ASqSOFA (for in-hospital mortality: 0.812; 95% CI: 0.789-0.835, for ICU admission: 0.794; 95% CI: 0.771-0.817), which included age and SpO2 with qSOFA, were simple and not inferior to other more complex models (e.g., ASMqSOFA, ASLqSOFA, and ASMLqSOFA). ASqSOFA also displayed significantly higher AUROC than other triage scales, such as the modified early warning score and Korean triage and acuity scale. The optimal cut-off score of ASqSOFA for the outcome was 2 and the score for redistribution to a lower-level emergency department was 0. Conclusion: We demonstrated that ASqSOFA can be employed as a simple and efficient triage tool for emergency febrile patients to aid in resource distribution during overcrowding. It may also be applicable in pre-hospital settings for febrile patient triage.
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PURPOSE: Alzheimer's disease (AD) is a heterogeneous disease that presents a broad spectrum of clinicopathologic profiles. To date, objective subtyping of AD independent of disease progression using brain imaging has been required. Our study aimed to extract representations of unique brain metabolism patterns different from disease progression to identify objective subtypes of AD. METHODS: A total of 3620 FDG brain PET images with AD, mild cognitive impairment (MCI), and cognitively normal (CN) were obtained from the ADNI database from 1607 participants at enrollment and follow-up visits. A conditional variational autoencoder model was trained on FDG brain PET images of AD patients with the corresponding condition of AD severity score. The k-means algorithm was applied to generate clusters from the encoded representations. The trained deep learning-based cluster model was also transferred to FDG PET of MCI patients and predicted the prognosis of subtypes for conversion from MCI to AD. Spatial metabolism patterns, clinical and biological characteristics, and conversion rate from MCI to AD were compared across the subtypes. RESULTS: Four distinct subtypes of spatial metabolism patterns in AD with different brain pathologies and clinical profiles were identified: (i) angular, (ii) occipital, (iii) orbitofrontal, and (iv) minimal hypometabolic patterns. The deep learning model was also successfully transferred for subtyping MCI, and significant differences in frequency (P < 0.001) and risk of conversion (log-rank P < 0.0001) from MCI to AD were observed across the subtypes, highest in S2 (35.7%) followed by S1 (23.4%). CONCLUSION: We identified distinct subtypes of AD with different clinicopathologic features. The deep learning-based approach to distinguish AD subtypes on FDG PET could have implications for predicting individual outcomes and provide a clue to understanding the heterogeneous pathophysiology of AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Aprendizaje Profundo , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Tomografía de Emisión de Positrones/métodos , Progresión de la Enfermedad , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismoRESUMEN
BACKGROUND AND AIM: Decreased kidney function is a putative risk factor for various cancers. However, few studies have investigated the association between a decreased estimated glomerular filtration rate (eGFR) and incident pancreatic cancer. We aimed to investigate the risk of incident pancreatic cancer according to eGFR categories. METHODS: In this retrospective cohort study, we included 359 721 adults who underwent health checkups in 2009 or 2010 by using the Korean National Health Insurance Database. The study population was categorized into four groups by eGFR (mL/min/1.73 m2 ) using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR < 45), group 2 (eGFR ≥ 45 to < 60), group 3 (eGFR ≥ 60 to < 90), and group 4 (eGFR ≥ 90). Multivariate Cox proportional hazards models were used to determine the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pancreatic cancer until 2019 by comparing the eGFR groups. RESULTS: During the 3 493 589.05 person-years of follow-up, 1702 pancreatic cancer cases were identified. Compared with group 4 (eGFR ≥ 90), HRs and 95% CIs for the incidence of pancreatic cancer were 1.39 (1.24-1.56) for group 3 (eGFR ≥ 60 to < 90), 1.79 (1.47-2.16) for group 2 (eGFR ≥ 45 to < 60), and 2.05 (1.62-2.60) for group 1 (eGFR < 45) in the multivariate adjusted model. CONCLUSIONS: Decreased eGFR was significantly associated with an increased risk of pancreatic cancer in Korean population. Further studies are needed to investigate the relationship between a decreased eGFR and the risk of pancreatic cancer in other ethnic groups.
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Neoplasias Pancreáticas , Insuficiencia Renal Crónica , Adulto , Humanos , Tasa de Filtración Glomerular , Estudios Retrospectivos , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/complicacionesRESUMEN
BACKGROUND: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. METHODS: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥ 55 years, including 276 cognitively normal older adults (CN), 142 with mild cognitive impairment (MCI), and 87 AD patients, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. RESULTS: Compared to CN, AD and MCI subjects showed significantly higher RD, MD, and AxD values (all p-values < 0.001) and significantly lower FA values (left p ≤ 0.002, right p ≤ 0.015) after Bonferroni adjustment for multiple comparisons. Most tests of cognition and mood (p < 0.001) as well as higher medial temporal amyloid burden (p < 0.001) were associated with poorer WM integrity in the CBH after Bonferroni adjustment. CONCLUSION: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Sustancia Blanca , Humanos , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/complicaciones , Sustancia Blanca/diagnóstico por imagen , Imagen de Difusión Tensora , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/complicaciones , Proteínas Amiloidogénicas , República de Corea/epidemiologíaRESUMEN
BACKGROUND: As tracking subtle cognitive declines in the preclinical stage of Alzheimer's disease (AD) is difficult with traditional individual outcome measures, need for cognitive composite for preclinical AD is widely recognized. OBJECTIVE: We aimed to develop culturally appropriate cognitive composite that sensitively identifies subtle cognitive decline of preclinical AD in Korean older adults. METHODS: A total 225 cognitively normal elderly individuals from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, were included. Tests of episodic memory, orientation, and executive function were carefully selected through review of previously established composites. Three candidate composites including Consortium to Establish a Registry for Alzheimer's Disease Word list recall (WLR), Logical memory (LM) II, and Mini-Mental status examination (MMSE) in common, and Letter fluency test (LF), category fluency test, or Stroop color and word test, were selected. RESULTS: Student t-tests demonstrated that only the composite composed of WLR, LM II, MMSE, and LF (Composite 1) showed a significant difference in score decline over two-year follow-up period between Aß positive and negative group (pâ=â0.03). Linear mixed model analyses also showed that the Aß x time interaction effect was significant only for Composite 1 (pâ=â0.025). Based on the results, Composite 1 was chosen as the final cognitive composite for preclinical Alzheimer's disease (CPAD). CONCLUSIONS: CPAD can be used to assess subtle cognitive decline of preclinical AD in clinical research settings, especially in Korean older adults. It also may be used for monitoring progression or treatment benefits in clinical practices.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Anciano , Enfermedad de Alzheimer/psicología , Progresión de la Enfermedad , Disfunción Cognitiva/psicología , Cognición , República de Corea , Pruebas Neuropsicológicas , Péptidos beta-AmiloidesRESUMEN
Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.
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BACKGROUND: Low body mass index (BMI) or underweight status in late life is associated with an increased risk of dementia or Alzheimer's disease (AD). However, the relationship between late-life BMI and prospective longitudinal changes of in-vivo AD pathology has not been investigated. METHODS: This prospective longitudinal study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). A total of 194 cognitive normal older adults were included in the analysis. BMI at baseline was measured, and two-year changes in brain Aß and tau deposition on PET imaging were used as the main outcomes. Linear mixed-effects (LME) models were used to examine the relationships between late-life BMI and longitudinal change in AD neuropathological biomarkers. RESULTS: A lower BMI at baseline was significantly associated with a greater increase in tau deposition in AD-signature region over 2 years (ß, -0.018; 95% CI, -0.028 to -0.004; p = .008), In contrast, BMI was not related to two-year changes in global Aß deposition (ß, 0.0002; 95% CI, -0.003 to 0.002, p = .671). An additional exploratory analysis for each sex showed lower baseline BMI was associated with greater increases in tau deposition in males (ß, -0.027; 95% CI, -0.046 to -0.009; p = 0.007), but not in females. DISCUSSION: The findings suggest that lower BMI in late-life may predict or contribute to the progression of tau pathology over the subsequent years in cognitively unimpaired older adults.
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Enfermedad de Alzheimer , Femenino , Masculino , Humanos , Anciano , Índice de Masa Corporal , Enfermedad de Alzheimer/diagnóstico por imagen , Estudios Longitudinales , Estudios Prospectivos , EnvejecimientoRESUMEN
BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.
Asunto(s)
Enfermedad de Alzheimer , Masculino , Humanos , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Estudios Transversales , Enfermedad de Alzheimer/tratamiento farmacológico , PadresRESUMEN
High blood adiponectin has been associated with Alzheimer's disease (AD) dementia and related cognitive decline. We aimed to investigate the association between serum adiponectin level and in vivo AD pathologies. Cross-sectional and longitudinal study designs for the data of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, an ongoing prospective cohort study that began in 2014. A total of 283 cognitively normal older adults between 55 and 90 years of age were included in community and memory clinic setting. Participants underwent comprehensive clinical assessments, measurement of serum adiponectin level, and multimodal brain imaging, including Pittsburgh compound-B positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and MRI at baseline and 2-year follow-up. Serum adiponectin level was positively associated with global beta-amyloid protein (Aß) retention and change therein over 2 years, but not with other AD neuroimaging markers including tau deposition, AD-related neurodegeneration, and white matter hyperintensities. Blood adiponectin level is associated with increased brain amyloid deposition, which suggests that adiponectin may be a potential target for therapeutic and preventive strategies against AD.